Cognitive impairment after surgery occurs frequently in the large number of increasingly elderly patients undergoing cardiac surgery every year. Postoperative cognitive deficit (POCD) is present in 36-50% of patients in the early phases after surgery and has been shown to adversely impact quality of life as much as one year after surgery. Despite substantial advancement in technology, pharmacology, and perioperative organ protection leading to reductions in mortality associated with cardiac surgery, the incidence of POCD has changed little over the last ten years. While multiple etiologic factors have been proposed for this neurological injury including cerebral embolic processes and hypoperfusion, it is likely that the degree of dysfunction is significantly modulated by the inflammatory responses that define ischemia and reperfusion. The objective of our multidisciplinary Neurological Outcome Research Group (NORG) is to understand the mechanisms underlying neurologic and neurocognitive dysfunction after cardiac surgery and to reduce the incidence of these devastating outcomes. Recently we administered lidocaine as an infusion during and after cardiac surgery and found preliminary data for a protective effect of lidocaine against POCD in non-diabetic subjects. We believe that intravenous lidocaine at antiarrhythmic doses offers neuroprotection by membrane stabilization and prevention of ion flux during initial vessel occlusion, followed by amelioration of the secondary inflammatory changes. Thus the primary aim of our prospective, randomized, double-blind interventional clinical trial is to determine the effectiveness of lidocaine in reducing postoperative cognitive decline. Secondarily, we will determine the effect of lidocaine upon the inflammatory response across the cerebral vasculature by measuring the jugular-arterial monocyte, polymorphonuclear, and platelet activation gradients. Little is more devastating to a patient or the patient's family than to have a successful operation that prolongs life but diminishes the quality of that life. Nothing is more likely to adversely impact quality of life than deterioration in a patient's neurocognitive status with resultant loss of independence. With the large number of patients still undergoing cardiac surgery, a simple and inexpensive intervention such as intravenous lidocaine holds the potential of dramatically increasing the quality of life for hundreds of thousands of patients world- wide. PUBLIC HEALTH RELEVANCE: Cognitive impairment is a common complication of cardiac surgery. In this research proposal, we plan to use lidocaine, an inexpensive and commonly available drug, to reduce postoperative cognitive dysfunction. The use of lidocaine therapy holds great promise for improving cognitive function and as a consequence, quality of life and functional independence for the large number of our increasingly elderly patients.